FIGS. 1 through 5 show conventional typical administration methods and efficacy rates of anticancer drugs. FIG. 1 is a table showing conventional administration methods and efficacy rates of methotrexate. FIG. 2 is a table showing conventional administration methods 5-fluorouracil. FIG. 3 is a table showing a randomized trial result of various treatments that have been conventionally practiced in Japan, Europe and the United States. FIG. 4 is a table showing conventional administration methods of vincristine. FIG. 5 is a table showing remission rates for various malignant tumors in conventional administration methods.
All administration methods shown in FIGS. 1 through 5 are methods that perform injections or drip injections, take drug holidays for weeks until a side effect of administrations disappears, and repeat the administrations (see, for example, Non-patent Document 1 and Non-patent Document 2).
However, the conventional administration methods shown in FIGS. 1 through 5 have had a problem of anticancer drugs not being able to exert their effectiveness sufficiently because drug solutions are administrated at arbitrary timing without respect to a cell cycle of a cancer cell. This regard is discussed in detail below with reference to accompanying drawings.
FIG. 6 is a diagram showing an example of a cell cycle. The cell cycle is a concept of viewing a process where the cells divide and the number of cells doubles as a single cycle. The cell cycle is formed of a cycle composed of respective phases including a DNA synthesis preparation phase (i.e., nymphochrysalis: G1 phase), a DNA synthesis phase (S phase), a cell division preparation phase (imagochrysalis: G2 phase), and a cell division phase (M phase). Here, cells that temporarily or reversibly stop the cell division are regarded to be in a stationary phase called G0 phase. A single cancer cell doubles by completing the cell cycle, and continues to doubly increase. The anticancer drug is a generic name of a medical drug, agent or substance that has a function of inhibiting proliferation of the cancer cells, and is roughly divided into two kinds, a time-dependent type drug and a concentration-dependent type drug. The time-dependent type drug shows its effectiveness related to the cell cycle.
It is thought that the time-dependent type anticancer drug effectively acts on G1 phase of the cell cycle shown in FIG. 6, and shows the effectiveness by putting a brake on the progress. The cancer is composed of many cancer cells, and the respective cancer cells are in different phases of the cell cycle. Therefore, even if the anticancer drug is administered in certain timing, the effectiveness of the anticancer drug can be obtained only to the cancer cells in G1 phase at the administered timing, and the anticancer drug cannot produce the effect on the cells in the other phases.
Here, if the cell cycle of the cancer cells is made T, and a period of G1 phase where the anticancer drug can produce the effect is made t, when the anticancer drug at first is administered in a certain timing, a ratio of the number of cells that the anticancer drug can prevent the cell division is t/T to all cells, and a rate of the number of cells that escape from the effect is (T−t)/T to all cells. If the conventional administration methods are repeated n times (where n is an integer), a ratio of the number of cells that escape from the effect after n times is ((T−t)/T)n.
As an example, if the cell cycle T is made 24 h; G1 phase t is made 4 h; and the number of administration is made six times, it is found that (20/24)6=0.3349=33.5% of the cancer cells remain.
That means that the conventional administration methods have a problem of not being able to exclude the cancer cells that escape from the inhibitory effect in theory, even if the frequency of administration is increased.
Furthermore, because a continuous administration time is long, there is a problem of a physical and mental strain of a patient who receives a dose being great. More specifically, since a small amount of anticancer drug is diluted with a solution, and a treatment is carried out by giving the patient a drip continuously for a long time, the patient comes to take large volumes of fluid. Because of this, the patient has to go to a restroom frequently, which causes a large burden to the patient. Moreover, because the conventional administration methods impose on the kidneys of the patient, there has been a problem of not being able to perform the administration to the patient having a kidney disorder. In addition, if the administration is performed by hospital visit, the best timing can be midnight, depending on the administration timing. In this case, there has been a problem of the administration being a burden for both of a healthcare professional and the patient.
[Non-patent Document 1] “Anticancer Report: Fluorouracil and Leucovorin (Colorectal cancer)”, online, Aug. 11, 2010 searched, Internet, <URL:http://www.mhlw.go.jp/shingi/2004/05/dl/s0521-5o.pdf>
[Non-patent Document 2] “Oncovin”, online, Aug. 11, 2010 searched, Internet <URL: http://www.info.pmda.go.jp/go/pack/4240400D1030—2—06/>